Scavenging effects of hemoglobin and related heme containing compounds on nitric oxide, reactive oxidants and carcinogenic volatile nitrosocompounds of cigarette smoke. A new method for protection against the dangerous cigarette constituents

Abstract

The present study refers to the utilization of hemoglobin and related heme containing substances in scavenging noxious compounds contained in the gas phase of cigarette smoke (e.g. nitric oxide (NO), nitrogen oxides (NOx), hydrogen peroxide (H2O2), carbon monoxide (CO), aldehydes, trace elements and carcinogenic nitrosocompounds) which were up to today insufficiently retained by conventional cigarette filters. Hemoglobin impregnated conventional cigarette filters were capable of withholding the above noxious components of the cigarette smoke up to 90%. Similar results were also obtained when solid hemoglobin was sandwiched between two common filters so that all cigarette smoke drawn through the filter comes into contact with the active groups of the hemoglobin molecules (Fe3+, Fe2+, -SH, -NH2). The present study also shows that noxious oxidants contained in cigarette smoke can be retained and neutralized by appropriate scavengers like: a) substances which contain stereospecifically bound iron, b) substances which contain porphyrin ring with iron (e.g. protoporphyrin), c) substances which contain porphyrin ring that does not necessarily contain iron, d) substances which contain porphyrin ring complexed with other metals (e.g. Cu2+, Mg2+). We have also demonstrated that rat alveolar macrophages challenged by cigarette smoke release both superoxide (O2-) and NO the interaction of which resulted in the formation of peroxynitrite (ONOO-). Alveolar macrophages continue to release NO/ONOO- for 30 min following two or three puffs of smoke. Similar results were also obtained in experiments with human volunteers. It was shown that during cigarette smoking the ratio of NO/ONOO- in the inhaled smoke was 1:0.5 while in the exhaled smoke was 1:9, due to secondary redox reactions taking place in the lung resulting in the ONOO- formation. When smokers inhaled cigarette smoke passed through a conventional filter containing hemoglobin, a 70% reduction of both NO and ONOO- in their exhaled cigarette smoke was observed. All findings prove conclusively that, alveolar macrophages exposed to cigarette smoke evoke a dramatic increase of NO, NOx, ONOO- and H2O2 inside the lung. These substances stimulate by a positive feed back mechanism the alveolar macrophages and perhaps even endothelium of the alveolar vessels, to produce more oxidants resulting in lung damage.